This project includes several studies designed to examine genetic influences and gene-environment interaction with respect to childhood respiratory illness in several different populations throughout the world with different prevalences of asthma. In the spring of 1998, we began collection of buccal cells, as a source of DNA for genetic analysis, among children enrolled in a cohort study of health effects of air pollution in Southern California (USC Children's Health Study). This project is now being coordinated with an extramurally funded grant. We are also involved in analysis of data from the children's health study. We are beginning work to initiate a study of genetic susceptibility to childhood asthma among inner city residents of Mexico City. We plan to enroll 160 asthmatic children and their parents in a study of candidate gene associations for asthma in FY 99 and expand the study in FY00. The use of parent child trio enables assessment of candidate gene associations in a setting free from population stratification, a potential bias in genetic studies in heterogeneous populations, such as in Mexico City. We also are beginning a collaboration to collect buccal cell samples on 5000 middle school children in Wuhan , China who are being enrolled in a cohort study to examine smoking and health outcomes including pulmonary function and respiratory symptoms. Nested case-control studies will be done to examine candidate gene association with asthma, chronic respiratory symptoms and impaired growth in pulmonary function. Wuhan China is a low asthma incidence area (estimate of 1-2.5% prevalence). Mexico City is has intermediate rates (about 4%) whereas the Southern California population has the high rates seen in recent US studies (about 10%). Both the Wuhan and Mexico City populations are exposed to high levels of particles other ambient air pollutants as well as antigens such as cockroach, believed to be involved in asthma etiology. The study of populations with high and low incidence of asthma can help identify which proposed risk factors for asthma are etiologically related to the disease.